As is known, the treatment of some fluids involves an increasingly precise temperature regulation, in particular when chemical or biochemical reactions are involved. Furthermore, it is frequently necessary to use very small amounts of fluid, since the fluid is costly or not always readily available.
This is, for example, the case of the DNA-amplification process (polymerase chain reaction process, also called a PCR process) wherein precise temperature control in the various phases (it is necessary to repeatedly perform preset thermal cycles), the need to avoid as far as possible thermal gradients in the reaction areas of the fluid (to have uniform temperature in these areas), and also the quantity of fluid used (which is very costly) are of crucial importance for obtaining good reaction efficiency or even for obtaining the reaction itself.
Other examples of treatment of fluids having the characteristics indicated above are, for instance, linked chemical and/or pharmacological analyses, biological tests, etc.
At present, various techniques are available that enable thermal control of chemical or biochemical reagents. A first technique uses a reactor including a glass or plastic base on which a biological fluid is deposited through a pipette. The base rests on a hot-plate called “thermo-chuck,” which is controlled by external instrumentation.
Another known reactor comprises a heater, which is controlled by appropriate instrumentation and on which a biological fluid to be examined is deposited. The heater is supported by a base which also carries a sensor arranged in the immediate vicinity of the heater and is also connected to the instrumentation for temperature regulation, so as to enable precise control of the temperature.
Both types of reactors are often enclosed in a protective casing.
A common disadvantage of the known reactors lies in the large thermal mass of the system; consequently, they are slow and have high power absorption. For example, in the case of the PCR process mentioned above, times of the order of 6–8 hours are required.
Another disadvantage of known solutions is linked to the fact that, given the macroscopic dimensions of the reactors, they are able to treat only relatively high volumes of fluids (i.e., minimum volumes of the order of milliliters).
The disadvantages referred to above result in very high treatment costs (in the case of the aforementioned PCR process, the cost can amount to several hundreds of dollars); in addition, they restrict the range of application of known reactors to test laboratories alone.
To overcome the above mentioned drawbacks, starting from the late eighties miniaturized devices of reduced thermal mass have been developed and allow a reduction in the times required for completing the DNA-amplification process.
The first of these devices is described in the article by M. A. Northrup, M. T. Ching, R. M. White, and R. T. Watson, “DNA amplification with a microfabricated reaction chamber,” Proc. 1993 IEEE Int. Conf. Solid-State Sens. Actuators, pp. 924–926, 1993, and comprises a reactor cavity formed in a substrate of monocrystalline silicon by anisotropic etching. The bottom of the cavity comprises a thin silicon-nitride membrane, on the outer edge of which are heaters of polycrystalline silicon. The top part of the cavity is sealed with a glass layer. Thanks to its small thermal mass, this structure can be heated at a rate of 15° C./sec., with cycling times of 1 minute. With this device it is possible to carry out, for a volume of fluid of 50 μl, twenty amplification cycles in periods approximately one fourth the time required by conventional thermocyclers and with a considerably lower power consumption.
However, the described process (as others currently used based on bonding of two silicon substrates previously subjected to anisotropic etches in KOH, TMAH, or other chemical solutions) is costly, has high critical aspects and low productivity, and is not altogether compatible with the usual manufacture steps used in microelectronics.
Other more recent solutions includes forming, inside a first wafer of semiconductor material, buried channels connected to the surface via inlet and outlet trenches, and, inside a second wafer of semiconductor material, reservoirs formed by anisotropic etching, and bonding together of the two wafers.
Also this solution, however, is disadvantageous in that the process is costly, critical, has low productivity, and requires the use of a glass frit for bonding the two wafers together.